Arsenic trioxide

Arsenic trioxide is injected into a vein through an IV. A healthcare provider will give you this injection.

While using arsenic trioxide, you may need frequent blood tests at your doctor's office. Your heart function may need to be checked using an electrocardiograph or ECG (sometimes called an EKG).

You must remain under the care of a doctor while you are using arsenic trioxide. Do not miss any follow-up appointments.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss an appointment for your arsenic trioxide injection.

Some patients with acute promyelocytic leukemia (APL) have cancer cells that express a certain gene known as PML/RAR-alpha. These cancer cells may also have a change (or a mutation) in chromosomes 15 and 17. Chromosomes are structures that carry the genetic information of a cell. When these specific genes are present, the cells divide more rapidly.  

Testing for the PML/RAR-alpha gene and chromosomes 15/17 mutations are done to determine whether aresenic trioxide is likely to be an effective treatment for APL. If the cancer cells do not test positive for least one of these genes, arsenic trioxide may not be an effective treatment.

Arsenic trioxide is approved for the treatment of APL in patients whose leukemia cells test positive for the PML/RAR-alpha gene or the chromosomes 15/17 mutations. Arsenic trioxide targets and breaks down the PML-RAR-alpha gene, which helps slow the growth of leukemia cells.  

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. One patient who became pregnant while receiving arsenic trioxide had a miscarriage. It is advisable to avoid pregnancy while on this medication. Arsenic trioxide may cause harm the the fetus (unborn baby).

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.
 

Since this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.
 

Pregnancy Category: D

Lactation: Arsenic is excreted in milk. Because of the potential for serious adverse reactions in nursing infants from this drug, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

IV Incompatibilities

Do not mix with other medications

IV Preparation

Dilute in 100-250 mL D5W or NS

Does not contain a preservative; properly discard unused portion

IV Administration

Infuse over 1-2 hr

If acute vasomotor reactions occur, may infuse over a maximum of 4 hr

Does not require administration via a central venous catheter

Storage

Store at room temp; do not freeze

Call your doctor for instructions if you miss an appointment for your arsenic trioxide injection.

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.1

Administration

Administer by IV infusion.1

IV Administration

For solution compatibility information, see Compatibility under Stability.

IV solutions of the drug contain no preservatives; discard any unused portion of single-use ampul.1

Do not mix with other drugs.1

Immediately after withdrawing the appropriate dose of the drug from the ampul, dilute with 100–250 mL of 5% dextrose injection or 0.9% sodium chloride injection.1

Administer by IV infusion over 1–2 hours; if acute vasomotor reactions occur, longer infusion periods (e.g., up to 4 hours) may be used.1

Dosage

Pediatric Patients

In children ≥5 years of age, 0.15 mg/kg daily.1 Continue until bone marrow remission occurs or for a maximum of 60 doses.1

In children ≥5 years of age, 0.15 mg/kg daily for 25 doses, administered over a period of up to 5 weeks.1 Initiate 3–6 weeks after completion of induction therapy.1

Adults

0.15 mg/kg daily.1 Continue until bone marrow remission occurs or for a maximum of 60 doses.1

0.15 mg/kg daily for 25 doses, administered over a period of up to 5 weeks.1 Initiate 3–6 weeks after completion of induction therapy.1

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Dizziness.
• Headache.
• Belly pain.
• Hard stools (constipation).
• Loose stools (diarrhea).
• Not hungry.
• Weight gain or loss.
• Feeling tired or weak.
• Dry mouth.
• Not able to sleep.
• Feeling sleepy.
• Bone, joint, or muscle pain.
• Back pain.
• Sweating a lot.
• Pain where the shot was given.
• Redness or swelling where the shot is given.
• Eye irritation.
• Anxiety.
• Pain in arms or legs.
• Dry skin.
• Flushing.
• Neck pain.
• Pale skin.
• Skin irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Induces apoptosis in APL cells via morphological changes and DNA fragmentation; also damages or degrades the fusion protein promyelocytic leukemia (PML)-retinoic acid receptor (RAR) alpha

Distribution

Vdss: Arsenious acid (AsIII): 562 L; widely distributed throughout body tissues; dependent on body weight and increases as body weight increases; orally administered arsenic trioxide distributes into the CNS

Metabolism

Arsenic trioxide is immediately hydrolyzed to the active form, arsenious acid (AsIII) which is methylated (hepatically) to the less active pentavalent metabolites, monomethylarsonic acid (MMAv) and dimethylarsinic acid (DMAv) by methyltransferases; AsIII is also oxidized to the minor metabolite, arsenic acid (Asv)

Excretion

Urine (MMAv, DMAv, and 15% of a dose as unchanged AsIII)

Time to Peak

AsIII: At the end of infusion (2 hours); MMAv and DMAv; ~10 to 24 hours

Half-Life Elimination

AsIII: 10 to 14 hours; MMAv: ~32 hours; DMAv: ~72 hours

Consider delaying infusion if a severe non-hematologic reaction occurs (eg, neurologic or dermatologic toxicity) until the toxicity has improved to ≤ grade 1.

Administration Advice:
-May extend IV infusion duration up to 4 hours if vasomotor reactions are observed; a central venous catheter is not required.

Storage Requirements:
-Consult the manufacturer product information.

Reconstitution/Preparation Techniques:
-Consult the manufacturer product information.

IV Compatibility:
-Do not mix this drug with other medications.

General:
-Overdosage management: Consult the manufacturer product information.

Monitoring:
-Cardiovascular: ECG, QT/QTc interval, heart beat
-Laboratory: Electrolytes, creatinine, glucose; hepatic, renal, hematologic, and coagulation profiles
-Nervous System: Neuropathy signs/symptoms
-Oncologic: APL differentiation syndrome signs/symptoms; development of second primary malignancies.